The general goal of the Program is to determine the blood and blood vessel interacting components responsible for the pathogenesis of occlusive vascular disease. One basic model is the rabbit or rat aorta that has been de-endothelialized by passage of a balloon catheter, and which develops atherosclerosis even without dietary lipid supplement. Lesions are prevented or moderated by platelet-depressing agents, and studies will be directed to identifying the site of origin, the nature, and the mechanism of action of the various participating components. Recently, the tissue culture technique has been added to provide ex-vivo support for these studies. A second approach has been study of the mechanisms involved in endothelial cell attachment and detachment to the vessel wall. Current data suggest that endothelial cells are passively attached to the subendothelium, and studies are in progress to define the nature of the bond. The present approach is to perfuse rabbit aortas with different enzymes, in an attempt to characterize the respective substrate. Concurrently, the spectrum of enzymes of the blood vessel cells is being explored. A third area of endeavor is characterization of platelet-vessel wall interaction. Both the platelets and plasma are being investigated for major reacting components. Specifically, the studies concern the role of platelet rod myosin in the adhesion reaction, and the participation of von Willebrand factor in this process.